Antiplatelets, Anticoagulants & Thrombolytics 1 Flashcards
3 classes of drugs that keep platelets in control
- Anti-platelet
- Anti-coagulant
- Fibrinolysis
Which polymorphisms must you be aware of in platelet drugs (2)?
- warfarin
- clopidogrel
Where do platelet clotting factors assemble?
On the surface of platelets → change shape to spiny structure increasing surface area & charge. This helps the factors assemble and expose phosphatidyl C ring → Ca2+ binds surface & clotting factors
(w/o activation → no clotting)
Aspirin MOA
Irreversible inhibition of COX-1 & COX-2 → suppress thromboxanes & prostaglandins
How does Aspirin inhibit COX enzymes
attaches acetyl group → steric hindrance → cannot come into contact w/arachidonic acid → no Thromboxane A2
Aspirin indications (2)
- TIA
- Acute coronary syndrome (NSTEMI or STEMI MI)
(fever, pain & headache)
Aspirin contraindications (5)
- GI ulcer
- Hx of asthma
- Children: chicken pox of flu → reye’s syndrome
- Combo w/methotrexate
- Last trimester of pregnancy
Why can aspirin not be used w/methotrexate (15 mg/week)?
reduces methotrexate elimination → decreases renal clearance & displaces it from protein binding sites → hematologic toxicity
Why is aspirin not given to women in the 3rd trimester of pregnancy?
acetylation of fetal enzymes
How does aspirin cause GI bleeding?
blocking prostaglandin synthesis → decreased renewal of epithelium cells → decreased mucus production & protection of the stomach lining.
Aspirin Adverse Effects (7)
- Hemolytic anemia
- Bleeding: GU, gingiva
- GI inflammation, heartburn
- Asthma, anaphylaxis, nasal congestion
- Mental confusion, drowsiness
- Tinnitis, hearing loss
- Dizzy, vertigo
Hemolytic anemia may occur when ______ patients are given aspirin
G6PD deficient
At low dose, aspirin _____ (increases/decreases) gout attack; high dose ______ (increases/decreases) the risk of gout attack.
- increases
- decreases
P2Y12 receptor antagonist MOA: stops GPIIb/IIIa activation → decreases platelet aggregation by ______ (2).
- decreases Ca release
- increases cAMP levels
Clopidogrel MOA
- prodrug metabolized by CYP2C19
- Irreversible blocks ADP receptor on platelets (lasts 7 days; life of platelet)
(dose-dependent; metabolized by CYP450)
Clopidogrel drug interactions (3)
- CYP2C19 inhibitors (omeprazole or Esomeprazole)
- Opioids
- Repaglinide
(may need to genotype your patient first)
Prasugrel is a prodrug, like clopidogrel, and is converted to active metabolite by _____ (2) enzymes. It irreversibly inhibits ______.
- CYP3A4, CYP2B6
- P2Y12
(indicated for acute coronary syndrome)
Prasugrel contraindications (2)
- pathological bleeding
- Hx TIA/stroke
Which 2 P2Y12 antagonists are reversible inhibitors?
- ticagrelor (also p-glycoprotein inhibitor)
- Cangrelor
(clopidogrel & prasugrel are irreversible inhibitors)
Which is the only antiplatelet drug that is NOT given orally?
Cangrelor (IV)
Why would you give cangrelor instead of another P2Y12 antagonist?
hepatic disease; this drug is not metabolized by the liver
How do GP2b/3a inhibitors work?
prevents fibrinogen from binding and bringing platelets together
GP2b/3a inhibitors
- Abciximab
- Eptifibatide
Abciximab is intended for use with _______ (2)
- aspirin
- heparin
(for coronary intervention)
Abciximab is a chimeric human-murine monoclonal ab against glycoprotein 2b/3a receptor of platelets. It is produced by _______.
continuous perfusion in mammalian cells
Abciximab onset?
Platelet recovery?
- rapid: half-life < 10 min
- platelet recovery w/in 48 hours
Thrombin inhibitors bind to ______. Why is this receptor unique?
- PAR1
- Carriers its own ligand (it just needs enzyme to cleave it → activation)
Vorapaxar is indicated for patients w/______.
hx of MI or peripheral artery disease
Vorapaxar MOA
thrombin inhibitor: reversible antagonist of PAR-1 (protease-activated receptor-1)
(long half life: 4 weeks!)
Cilostazol indicated to reduce _______
symptoms of intermittent claudication
Cilostazol MOA
inhibits phosphodiesterase III activity → inhibits platelet aggregation & vasodilation
Cilostazol contraindications
heart failure
Cilostazol: AE
- tachycardia, palpitations
- thrombocytopenia
- leukopenia
What is the major targets of coagulation inhibition (2)?
- Prevention of Thrombin IIa formation (inhibiting Xa)
- second most effective is factor X
INR measures _____
warfarin activity
(PT monitors this as well)
Normal prothrombin time
11-15 seconds
(prolonged in patients on warfarin; may double)
INR =
PT patient/ PT normal)ISIS
(ISI determined by manufacturer of thromboplastin reagent)
Typical INR range
1.1
INR range of _____is an effective therapeutic range for warfarin
2-3
aPTT (activated partial thromboplastin time) uses (2)
- heparin activity
- investigate bleeding disorders
Normal PTT
35 seconds
How is [heparin] measured?
Anti-Xa activity
Which 2 classes of drugs are Direct/Novel Oral Anticoagulants (DOAC/NOAC)?
- Factor Xa inhibitors
- Thrombin (Factor IIa) inhibitors
List the factor Xa inhibitors (4)
- Apixaban
- Rivaroxaban
- Edoxaban
- Betrixaban
(the -“xaban”s)
List the thrombin (factor IIa) inhibitor
Dabigatran
RivaroXAban reduces the risk of _______ & treats ______ (2).
- stroke, systemic embolism in nonvalvular a-fib
- DVT, pulmonary embolism
Patients with a renal clearance < ______mL/min should not use RivaroXAban. Why?
- 15
- excretion is mainly via tubular & glomerular filtration
RivaroXAban discontinuation may increase risk of ______
stroke in nonvalvular a-fib
(Dabigatran also increases risk of thrombotic events if d/c early)
ApiXAban recommended dosage
5 mg 2xs/daily
ApiXAban contraindications (2)
- Pregnancy & Lactation
- Severe hepatic impairment
ApiXAban should NOT be used with ______ (Rx)
ELIQUIS
(P-gp & strong CYP3A4 inhibitors also)
ApiXAban BetriXAban & EdoXAban inhibit _____(2).
- free & clot-bound FXa
- prothrombinase activity
EdoXaban reduces risk of _____
stroke & PE in patients w/nonvalvular a-fib
